This is a combined clinical and experimental program designed to elucidate the regulation of hypophysiotropic and other brain peptides in relation to disease. We plan to study the factors that regulate prolactin hypersecretion in patients with the galactorrhea/amenorrhea syndrome, regulation of somatostatin secretion as influenced by hormones and neurotransmitters, utilizing isolated dispersed cells from cerebral cortex, hypothalamus and spinal cord of the rat, elucidation of the molecular biological basis of somatostatin synthesis, and the regulation of post-translational processing of somatostatin in brain. We are initiating a study of the secretion of LHRH in human milk, and in the cyst fluid of fibrocystic breast disease, both from the standpoint of its use as a tumor marker, and also for studying the hormonal regulation of LHRH secretion and synthesis in breast tumor tissue. We continue to study the effects of ACTH on infantile spasms (an idiopathic seizure disorder of young children), and attempt to differentiate between the direct effect of the peptide and the indirect effects of hypercortisolism produced by the ACTH. We also continue to develop hybrid proteins of diphtheria toxin and THR and somatostatin, in attempt to create a toxic compound targeted only to specific cell types by the particular receptors available.